The Multimodal Management of Locally Advanced Rectal Cancer: Making Sense of the New Data

In the past 40 years, the treatment of locally advanced rectal cancer has evolved with the addition of radiotherapy or chemoradiotherapy and providing (neo)adjuvant systemic chemotherapy to major surgery. However, recent trends have focused on improving our ability to risk-stratify patients and tailoring treatment to achieve the best oncologic outcome while limiting the impact on long-term quality of life. Therefore, there has been increasing interest in pursuing a watch-and-wait approach to achieve organ preservation. Several retro- and prospective studies suggest safety of the watch-and-wait approach, though it is still considered controversial due to limited clinical evidence, concerns about tumor regrowth, and subsequent distant progression. To further reduce treatment, MRI risk stratification, together with patient characteristics and patient preferences, can guide personalized treatment and reserve radiation and chemotherapy for a select patient population. Ultimately, improved options for reassessment during neoadjuvant treatment may allow for more adaptive therapy options based on treatment response. This article provides an overview of some major developments in the multimodal treatment of locally advanced rectal cancer. It reviews some relevant, controversial issues of the watch-and-wait approach and opportunities to personally tailor and reduce treatment. It also reviews the overall neoadjuvant treatment, including total neoadjuvant therapy trials, and how to best optimize for a potential complete response. Finally, it provides an algorithm as an example of how such a personalized, tailored, adaptive, and reduced treatment could look like in the future.